背景:本研究旨在探讨双醋瑞因(DIC)对多囊卵巢综合征(PCOS)小鼠模型内分泌和心脏代谢变化的影响。
方法:共有18只成年雌性小鼠(Parkes品系),年龄4-5周,被随机分配到三组,每个包括6只动物,如下:第一组(对照),接受正常饮食和生理盐水作为载体,持续51天;第二组接受来曲唑(LET;6mg/kgbw),持续21天诱导PCOS;第三组接受LET,然后每天口服灌胃DIC(35mg/kgbw),持续30天。
结果:这项研究表明,LET治疗导致PCOS具有多囊卵巢等特征,睾酮升高,体重增加,内脏肥胖,高水平的胰岛素以及空腹血糖,除了胰岛素抵抗,卵巢脂质处理不当,致动脉粥样硬化的血脂异常,受损的Na+/K+-ATP酶活性和血清,心脏,和卵巢氧化应激。在LET处理的小鼠中血清/卵巢脂联素水平降低。在用LET治疗的小鼠中,我们还发现心脏和血清对氧磷酶1(PON1)降低。有趣的是,DIC恢复了LET诱导的PCOS小鼠的卵巢和心脏代谢异常。DIC可以预防来曲唑诱导的PCOS小鼠的内分泌和心脏代谢变化。
结论:DIC对来曲唑诱导的PCOS并发氧化应激的改善作用,腹部脂肪沉积,心脏和卵巢基质处理不当,糖代谢功能障碍,脂联素/PON1激活支持DIC的观点,恢复PCOS中受损的内分泌和心脏代谢调节因子。
BACKGROUND: This study aimed to explore the impact of Diacerein (DIC) on endocrine and cardio-metabolic changes in polycystic ovarian syndrome (PCOS) mouse model.
METHODS: A total of 18 adult female mice (Parkes strain), aged 4-5 weeks, were randomly assigned to three groups, each comprising 6 animals, as follows: Group I (control), received normal diet and normal saline as vehicle for 51 days; Group II received Letrozole (LET; 6 mg/kg bw) for 21 days to induce PCOS; Group III received LET, followed by daily oral gavage administration of DIC (35 mg/kg bw) for 30 days.
RESULTS: This study indicates that treatment with LET resulted in PCOS with characteristics such as polycystic ovaries, elevated testosterone, weight gain, visceral adiposity, high levels of insulin as well as fasting blood glucose in addition to insulin resistance, improper handling of ovarian lipids, atherogenic dyslipidemia, impaired Na + /K + -ATPase activity and serum, cardiac, and ovarian oxidative stress. Serum/ovarian adiponectin levels were lowered in LET-treated mice. In mice treated with LET, we also discovered a reduction in cardiac and serum paraoxonase 1 (PON1). Interestingly, DIC restored ovarian andcardio-metabolic abnormalities in LET-induced PCOS mice. DIC prevented the endocrine and cardio-metabolic changes brought on by letrozole-induced PCOS in mice.
CONCLUSIONS: The ameliorative effects of DIC on letrozole-induced PCOS with concurrent oxidative stress, abdominal fat deposition, cardiac and ovarian substrate mishandling, glucometabolic dysfunction, and adiponectin/PON1 activation support the idea that DIC perhaps, restore compromised endocrine and cardio-metabolic regulators in PCOS.